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Pathway Description
Naltrexone Metabolism
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2022-04-26
Last Updated: 2023-10-25
Naltrexone is a narcotic antagonist used in opioid overdose. It is injected intravenously or intramuscularly. It travels through the blood to the target cells in the naltrexone pathway and to the liver. It is transported into the liver by an organic cation transporter. In the liver naltrexone is metabolized into 6-beta-naltrexol. It was predicted by biotransformer that Cytochrome P450 2C9 metabolizes naltrexone into 6-beta-naltrexol. However, it has also been found that Naltrexone in certain doses inhibits cytochrome enzymes. Only 2% of naltrexone remains as the original naltrexone while the remainder is metabolized into 6-beta-naltrexol and other minor metabolites. Naltrexone and 6-beta-naltrexol are transported out of the liver by organic cation transporters into the blood. It is then transported to the kidney where it is excreted renally. 53% to 79% of the dose is excreted as metabolites. A minor amount goes through bile to be excreted through the feces.
References
Naltrexone Metabolism References
Stancil SL, Abdel-Rahman S, Wagner J: Developmental Considerations for the Use of Naltrexone in Children and Adolescents. J Pediatr Pharmacol Ther. 2021;26(7):675-695. doi: 10.5863/1551-6776-26.7.675. Epub 2021 Sep 24.
Pubmed: 34588931
Krieter P, Chiang CN, Gyaw S, Skolnick P, Snyder R: Pharmacokinetic Interaction between Naloxone and Naltrexone Following Intranasal Administration to Healthy Subjects. Drug Metab Dispos. 2019 Jul;47(7):690-698. doi: 10.1124/dmd.118.085977. Epub 2019 Apr 16.
Pubmed: 30992306
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Hayer M, Bonisch H, Bruss M: Molecular cloning, functional characterization and genomic organization of four alternatively spliced isoforms of the human organic cation transporter 1 (hOCT1/SLC22A1). Ann Hum Genet. 1999 Nov;63(Pt 6):473-82. doi: 10.1017/S0003480099007770.
Pubmed: 11388889
Sakata T, Anzai N, Shin HJ, Noshiro R, Hirata T, Yokoyama H, Kanai Y, Endou H: Novel single nucleotide polymorphisms of organic cation transporter 1 (SLC22A1) affecting transport functions. Biochem Biophys Res Commun. 2004 Jan 16;313(3):789-93. doi: 10.1016/j.bbrc.2003.11.175.
Pubmed: 14697261
Itoda M, Saito Y, Maekawa K, Hichiya H, Komamura K, Kamakura S, Kitakaze M, Tomoike H, Ueno K, Ozawa S, Sawada J: Seven novel single nucleotide polymorphisms in the human SLC22A1 gene encoding organic cation transporter 1 (OCT1). Drug Metab Pharmacokinet. 2004 Aug;19(4):308-12.
Pubmed: 15499200
Meehan RR, Gosden JR, Rout D, Hastie ND, Friedberg T, Adesnik M, Buckland R, van Heyningen V, Fletcher J, Spurr NK, et al.: Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet. 1988 Jan;42(1):26-37.
Pubmed: 2827463
Kimura S, Pastewka J, Gelboin HV, Gonzalez FJ: cDNA and amino acid sequences of two members of the human P450IIC gene subfamily. Nucleic Acids Res. 1987 Dec 10;15(23):10053-4. doi: 10.1093/nar/15.23.10053.
Pubmed: 3697070
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
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